1,25-Dihydroxyvitamin D3 inhibits lipopolysaccharide-induced immune activation in human endothelial cells
Open Access
- 4 November 2005
- journal article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 143 (1), 58-64
- https://doi.org/10.1111/j.1365-2249.2005.02961.x
Abstract
In addition to its well‐known role in mineral and skeletal homeostasis, 1,25‐dihydroxyvitamin D3[1,25‐(OH)2, D3] regulates the differentiation, growth and function of a broad range of immune system cells, including monocytes, dendritic cells, T and B lymphocytes. Vascular endothelial cells play a major role in the innate immune activation during infections, sepsis and transplant rejection; however, currently there are no data on the effect of 1,25‐(OH)2 D3 on microbial antigen‐induced endothelial cell activation. Here we show that 1,25‐(OH)2 D3 pretreatment of human microvessel endothelial cells (HMEC) inhibited the enteric Gram‐negative bacterial lipopolysaccharide (LPS) activation of transcription factor NF‐κB and interleukin (IL)‐6, IL‐8 and regulated upon activation normal T cell exposed and secreted (RANTES) release. The effect of 1,25‐(OH)2 D3 was not due to increased cell death or inhibition of endothelial cell proliferation. 1,25‐(OH)2 D3 pretreatment of HMEC did not block MyD88‐independent LPS‐induced interferon (IFN)‐β promoter activation. 1,25‐(OH)2 D3 pretreatment of HMEC did not modulate Toll‐like receptor 4 (TLR4) or MD‐2 expression. These data suggest that 1,25‐(OH)2 D3 may play a role in LPS‐induced immune activation of endothelial cells during Gram‐negative bacterial infections, and a suggest a potential role for 1,25‐(OH)2 D3 and its analogues as an adjuvant in the treatment of Gram‐negative sepsis.Keywords
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